Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-κB Signaling after Nuclear DNA Damage.

DNA damage can be sensed as a danger-associated molecular pattern by the innate immune system. Here we find that keratinocytes and other human cells mount an innate immune response within hours of etoposide-induced DNA damage, which involves the DNA sensing adaptor STING but is independent of the cytosolic DNA receptor ...
cGAS. This non-canonical activation of STING is mediated by the DNA binding protein IFI16, together with the DNA damage response factors ATM and PARP-1, resulting in the assembly of an alternative STING signaling complex that includes the tumor suppressor p53 and the E3 ubiquitin ligase TRAF6. TRAF6 catalyzes the formation of K63-linked ubiquitin chains on STING, leading to the activation of the transcription factor NF-κB and the induction of an alternative STING-dependent gene expression program. We propose that STING acts as a signaling hub that coordinates a transcriptional response depending on its mode of activation.
Mesh Terms:
Ataxia Telangiectasia Mutated Proteins, Cell Line, Cell Nucleus, Cytosol, DNA, DNA Damage, HEK293 Cells, Humans, Immunity, Innate, Keratinocytes, Membrane Proteins, NF-kappa B, Nuclear Proteins, Phosphoproteins, Poly (ADP-Ribose) Polymerase-1, Signal Transduction, Tumor Suppressor Protein p53, Ubiquitin, Ubiquitin-Protein Ligases
Mol. Cell
Date: Dec. 06, 2017
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